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Virtual reality (VR) is a promising simulation medium for high-stakes, low-frequency events such as pediatric resuscitation. The psychological fidelity of VR compared with a real resuscitation in an emergency department (ED) is relatively unknown. The objective was to determine whether stress physiology changes were equivalent between ED and VR resuscitations.This was a single-site pilot equivalence study evaluating head-mounted VR resuscitation scenarios using board-certified/eligible pediatric ED physicians. Subjects had heart rates (HRs) and salivary cortisol levels recorded throughout 8-hour evening ED shifts and during one 1-hour VR session. Additional samples and subjective workload perception (NASA Task Load Index) were collected for critical resuscitations. A delta HR and delta cortisol level described the difference in mean HR and mean cortisol level between shifts with and shifts without resuscitations. Another delta calculation was performed from pre-VR to post-VR. Nonparametric univariate statistics was examined for significant differences in delta HR or cortisol levels between the ED setting and VR.Sixteen subjects had 69 shifts monitored with 31 resuscitations. In the ED, delta HR was +13.9 bpm (P < 0.001) and delta cortisol was +0.10 μg/dL (P = 0.006). In VR, delta HR was +6.5 bpm (P < 0.001) but minimal delta cortisol (−0.02 μg/dL, P = 0.05). Emergency department resuscitations both HR and cortisol levels were more than VR resuscitations (P < 0.03). NASA Task Load Index scores were higher in VR resuscitations with +26 score difference (P = 0.01).Virtual reality resuscitations increase HR but show less stress physiology changes than ED resuscitations within an actual 8-hour shift. Further inquiry into stress physiology and optimal VR simulation is warranted.